Capillary bridge in apparatus for determining ionic activity

ABSTRACT

A device is disclosed for determining ion activity in liquid solutions by the use of electrodes over which a cover sheet with an internal capillary bridge promotes ionic migration between the electrodes. The cover sheet is formed of a porous material ribbon encapsulated in a nonporous web. Preferably, the cover sheet is punched at each electrode to provide fluid access holes for receiving drops of liquid solutions.

CROSS REFERENCE TO RELATED APPLICATIONS

Reference is made to commonly assigned, copending U.S. patentapplication Ser. No. 927,085 entitled DEVICE FOR DETERMINING IONICACTIVITY, filed in the names of J. O. Paul and K. Babaoglu on July 24,1978, now U.S. Pat. No. 4,184,936.

BACKGROUND OF THE INVENTION

1. Field of the Invention

The present invention relates to devices useful in determining theactivity of an ionic analyte of an aqueous solution, and is particularlyuseful in potentiometrically measuring ion activity in drops ofbiological fluids.

2. Description of the Prior Art

There is a variety of apparatus in the prior art for measuring ionactivity in solutions. A test device incorporating ion-selectiveelectrodes which develop an electrical potential proportional to thelogarithm of the activity of the ions to which the electrodes aresensitive is described in the abovementioned commonly assigned U.S.patent application Ser. No. 927,085 and is shown at 10 in FIG. 1 of theaccompanying drawings. Two solid electrodes 12 and 14 are mounted on aframe 16, and a capillary bridge 18 is provided for promoting ionicmigration between two fluid access holes 20 and 22 at the electrodes.The capillary bridge includes a nonporous support layer, a porous layerwith ionic access to both electrodes, and a top nonporous cover layerwhich is preferably hydrophobic. When a drop of reference solution ofknown ion activity is applied to one fluid access hole and a drop oftest solution is applied to the other fluid access hole, the dropsspread into the porous layer until contact is made at a thin junctioninterface, permitting ionic migration between the drops. An electrometer24 is provided to measure the electrical potentials at the interfacesbetween each solution drop and its associated electrode to provide anindication of ion activity in the test solution.

Although the device disclosed in U.S. patent application Ser. No.927,085 provides excellent results in determining ion activity inliquids, the present invention is an improvement which providesadvantages in both assembly and performance. As can be seen in FIG. 1,capillary bridge 18 is a small discrete part which must be bothaccurately placed on the electrodes during assembly and held in place byan adhesive. These constraints increase assembly problems andpotentially decrease performance due to possible misalignment of thefluid access holes and failure of the adhesive bond. Further, fluidleakage from the edge of the bridge could affect the area of wettedelectrode surface because the edges of the bridge are aligned with theelectrodes. Unpredictability of the total area of wetted electrodesurface would adversely affect the test results.

SUMMARY OF THE INVENTION

In accordance with the present invention, a device is provided fordetermining the activity of an ionic analyte of an aqueous solutionwherein two electrodes are held in a frame by an integral cover sheetand capillary bridge. The cover sheet is formed of a nonporous materialwith an encapsulated porous ribbon, and fluid access holes extendthrough the cover sheet in alignment with the porous ribbon and eachelectrode. The test and reference fluids are confined to the porousribbon to form an ion junction between the electrodes.

In accordance with one embodiment of the present invention, the coversheet is formed by encapsulating a ribbon of porous material in thecross section of a plastic web by a two-pass extrusion process. Theporous material is located only in an area along a line generallycorresonding to the common centerline of both fluid access holes. Ventsare provided in the cover sheet to allow air in the bridge to bedisplaced by the advancing liquid wave fronts when test and referencesolutions are applied at the fluid access holes.

According to another embodiment of the present invention, the coversheet is formed by coating one side of a porous ribbon with a plasticmaterial and then pressing the coated ribbon into a film of nonporousmaterial.

The present invention permits assembly machines to be significantly lesscomplex because the assembled ion-selective electrode test device hasfewer components and the need to accurately locate a small discretecapillary bridge has been eliminated. As a result, test devicesmanufactured in accordance with the present invention exhibitexceptionally large drop placement latitude (i.e, a drop of liquid maybe placed upon the device anywhere over a large area and still wet theelectrode area) because the simplified assembly process allows the fluidaccess hole locations to be more accurately controlled. This feature isimportant in permitting relaxed manufacturing tolerances in automaticprocessing apparatus wherein the drops are applied mechanically.

Further, fluid leakage from the edge of the bridge will not affect thearea of wetted electrode surface because the edges of the bridge of thepresent invention are not aligned with the electrodes.

The invention, and its objects and advantages, will become more apparentin the detailed description of the preferred embodiments presentedbelow.

BRIEF DESCRIPTION OF THE DRAWINGS

In the detailed description of the preferred embodiments of theinvention presented below, reference is made to the accompanyingdrawings in which:

FIG. 1 is a perspective view of a device for determining the activity ofan ionic analyte of an aqueous solution constructed in accordance withthe prior art;

FIG. 2 is an exploded perspective view of a device for determining theactivity of an ionic analyte of an aqueous solution constructed inaccordance with the present invention;

FIG. 3 is an assembled sectional view taken generally along the linedesignated as 3--3 in FIG. 2;

FIGS. 4-7 are schematic illustrations of how one embodiment of the coversheet is fabricated;

FIGS. 8 and 9 are schematic illustrations of how another embodiment ofthe cover sheet is fabricated; and

FIG. 10 schematically shows the assembly of devices according to thepresent invention.

DESCRIPTION OF THE PREFERRED EMBODIMENTS

Although the invention as hereinafter described is directed to a devicefor potentiometrically determining ion activity through the use ofion-selective electrodes, such device can be used for other electricaltests of a liquid solution. The device is particularly adapted forprocessing by automated handling equipment.

FIG. 2 illustrates in exploded perspective a device 30 which has anelectrically insulative mounting frame 32 formed of a base web 34 and aspacer web 36. Two solid electrodes 38 and 40 are mounted in the frameand electrically isolated from each other. A cover sheet 42, with aninternal capillary bridge 44, promotes ionic migration between solutiondrops deposited in fluid access holes 46 and 48. The fluid access holesextend through the cover sheet in the region of electrodes 38 and 40.Two electrical access holes 50 and 52 are also formed in the coversheet.

The Electrodes

Electrodes 38 and 40 are either respectively an ion-selective electrodeand an external reference electrode, for a direct mode of determiningpotentials, or respectively two ion-selective electrodes for adifferential measurement comparing the ion activity of an unknown testsolution with that of a similar reference solution of known ionconcentration. Electrodes 38 and 40 are shown as being identical and,therefore, suitable for the differential mode of measurement which ismade be electrometer 24 (FIG. 1) when a test drop 54 (FIG. 3) is appliedto one electrode and a reference drop 56 having a known concentration ofions is applied to the other electrode. In FIG. 3, the thickness of thelayers of the electrodes has been greatly exaggerated for clarity.

Both electrodes are formed of layers comprising an ion-selectivemembrane 58 (permeable to the ion of choice) coated over a multilayerinternal reference element which in turn is coated over a support 60,all of which are solid layers. Each internal reference element is shownas comprising several layers such as metal layer 62, layer 64 which isan insoluble salt of the metal of layer 62, and layer 66 which is anelectrolyte containing layer. Although the layers are generally referredto as being "coated" one over another, it should be understood that theterm "coating" is meant to include laminating or otherwise forming thevarious strata one over another by any technique.

For purposes of describing the present invention, it is believed that adetailed discussion of the structure and operation of electrodes 38 and40 is not necessary. However, a full description of various embodimentsof such electrodes and the method of use thereof may be found inco-assigned U.S. Pat. No. 4,053,381. The disclosure of that patent isspecifically incorporated herein by reference.

The Cover Sheet and Capillary Bridge

Cover sheet 42 is shown in FIG. 2 and in section in FIG. 3. The coversheet is preferably a flat, composite web having through-holes 46, 48,50, and 52. A ribbon of porous material is encapsulated in the coversheet to form capillary bridge 44 between fluid access holes 46 and 48as a means of promoting ionic migration between electrodes 38 and 40.Bridge 44 in a preferred embodiment is a porous paper into which liquiddrops 54 and 56 are absorbed to form an ionic junction. A suitable paperfor correct absorption of human serum is Whatman #2 chroma, 0.007 inchthick, which is manufactured in the United Kingdom by W. and R. Balston,Ltd. When spotted with liquid solution drops at holes 46 and 48, theliquid fills the holes, forms large caps on cover sheet 42, and within10 to 30 seconds is absorbed into the paper. Another example of thematerial suitable for the porous ribbon is disclosed in referenced U.S.Pat. No. 4,053,381. However, other porous material which is resistant tobecoming clogged by the plastic overcoats will readily occur to thoseskilled in the art. Throughout this specification and the appendagedclaims, the porous material which forms capillary bridge 44 is referredto as a ribbon, and that is meant to define any elongated form such as,for example, a web, a thread, threads, a strip, etc.

The liquid from each drop spreads into capillary bridge 44 until contactis made at about the middle of the bridge to form an ionic junction.Preferably, sufficient liquid is left unabsorbed to fill holes 46 and48. It is desirable to vent the cover sheet to assure rapid junctionformation. Vents, such as shown at 67 in FIG. 3, allow air trapped inthe porous material to escape and be displaced by the advancing liquidwave fronts from the fluid access holes. Venting can be accomplished bypuncturing the top plastic covering to expose the porous material to theatmosphere. Optimally, vents should be spaced along the entire bridgearea between the fluid access holes. This design is better than havingvent holes only in the center of the bridge because in this latter case,the vent holes could be sealed off before liquid junction formation.This condition would be augmented when the flow rates from the test andreference drops were significantly different.

Capillary bridge 44 is preferably located only in an area along a linewhich corresponds to the common center-line of fluid access holes 46 and48. Generally, the porous material which forms the capillary bridgecannot be used as a full cover sheet because the additional volume wouldresult in too large a fluid capacity.

Operation

Operation of the device is described in U.S. Pat. No. 4,053,381, and ingeneral proceeds by spotting a drop of the reference solution in hole 46and a drop of the test solution in hole 48. Probes contact electrodes 38and 40 (FIG. 1), and the potentials are read on electrometer 24. Thereading indicates ion activity in the test solution.

The test device is then removed from contact with electrometer 24 anddisposed of, and a new device is positioned to receive subsequent dropsof solution and to contact the electrometer leads.

Cover Sheet Fabrication--First Embodiment

Reference is made to FIGS. 4-7 for a schematic illustration of thefabrication of an elongated web from which a plurality of cover sheets42 are produced. A roll 70 of suitable porous material for capillarybridge 44 is positioned ajdacent to an extrusion die 72, and the porousmaterial is drawn under the die into contact with a film 74 of moltenplastic. Film 74 may be polystyrene, but any plastic which can be formedinto a free film would be acceptable.

Before film 74 is completely quenched, the composite web of porousmaterial from roll 70 and plastic film 74 is calendered between a pairof rollers 76 and 78. The resultant composite web 80 has a uniformthickness (as shown in cross section in FIG. 5) and is wound into a roll82.

Referring to FIG. 6, composite web 80 is next unwound from roll 82 anddrawn under an extrusion die 84 into contact with another free film 86of molten plastic so that the side of web 80 into which the porousmaterial has been pressed is overcoated with a layer of plastic as theweb passes between rollers 88 and 90 and is wound into a roll 92. Across sectional view of the final web is shown in FIG. 7.

Several variations of the above process are within the scope of thepresent invention. For example, multiple parallel ribbons of porousmaterial can be encapsulated into a wide plastic web. The wide web wouldthen be split between the strands. Further, the need for a two-passoperation could be eliminated by use of multiple coating dies or acrosshead die.

Cover Sheet Fabrication--Second Embodiment

FIG. 8 is a cross-sectional view of a composite web formed in accordancewith another embodiment of the present invention. As shown in FIG. 9, aweb of porous material from a supply roll 86 is coated with polyethylenefrom an extrusion die 88. After the polyethylene has been quenched, theweb is slit into ribbons at 90 and wound into a plurality of rolls 92.

When the coated web of porous material is drawn under an extrusion diesimilar to die 72 of FIG. 4 and calendered with the polyethylene coatingfacing away from free film 74 of molten polystyrene, a composite web 93as shown in FIG. 8 is formed. In that figure, the porous material isdenoted by reference numeral 94, its polyethylene coating by numeral 96,and the quenched polystyrene base by numeral 98.

The cover sheet formed by this process has inherent ventilation becausethe polystyrene of base 98 does not bond to the polyethylene of coating96 during the extrusion process. The exposed porous material at the edgeof coating 96 provides a venting path to allow air to escape from thebridge as it is displaced by liquid absorbed by the bridge. Ifadditional venting is desired, it can be more easily implemented than inthe case of the FIGS. 4-7 embodiment because coating 96 is thinner thanthe second extrusion layer of the previous embodiment.

Assembly of the Device

The integral capillary bridge and cover sheet eliminates or simplifies anumber of slide assembly steps inherent in devices having discretebridges. Thus, assembly machines can be significantly less complex.

FIG. 10 schematically shows how the devices can be assembled when anintegral bridge and cover sheet is used. All of the materials except theion-selective electrodes are assembled by simply laminating continuouswebs of material together and chopping finished slides from theresulting web.

A web 100, which has been manufactured and slit in accordance with, forexample, any of the previously described embodiments, is coated at 101on one side with an adhesive and covered by an interleaving material102. This composite web is moved continuously in the direction of arrow104 past a set of punches 106 which moves cyclically to perforate theweb, forming round fluid access holes 46 and 48 and rectangularelectrical access holes 50 and 52 (FIG. 2).

Following punching station 106, interleaving material 102 is strippedfrom web 100 to expose the achesive coating. Ion-selective electrodes107, which are chopped from a web 108 by punches 110 and 111, areapplied to the adhesive in alignment with the fluid and electricalaccess holes. Punches 110 and 111 are close together when they punch web108 to eliminate waste. As the punches move toward web 100 to depositthe electrodes, the punches separate so that the electrodes are spacedapart. The adhesive coating on web 100 holds the ion-selectiveelectrodes in position and creates a seal around the fluid access holesto prevent the reference and sample fluids from spreading between thecover sheet and the ion-selective electrodes of FIG. 2.

A spacer web 112 is moved in the direction of arrow 114 from a stockroll, not shown. The spacer web has a plurality of ultrasonic energyconcentrators on its upper surface. The concentrators are schematicallyshown as lines c on web 36 in FIG. 2 and aid in the welding processspecified hereinafter. As web 112 passes under a pair of punches 116,rectangular holes 118 are punched to align with ion-selective electrodes107 on web 100 when the two webs join between a pair of rollers 120 and122.

A third web 124 also passes between rollers 120 and 122 to join with theother two webs. The third web also has ultrasonic energy concentrators cas shown schematically in FIG. 2 and forms base web 34 (FIG. 2) in thefinished device.

An ultrasonic horn or horns 126 and anvil or anvils 128 are movable intoengagement with, and then along with, the composite web to weld the webstogether. The presence of the high energy concentrators betweenindividual webs 100, 112, and 124 increase the welding operation'sefficiency.

The joined webs are translated from the welding station to a knife press130 by a continuously moving vacuum belt drive 132. Knife press 130 hasa rotary motion to chop the joined webs into individual slides which aremoved by a slide spacer belt 134 to a slide selecting vacuum belt 136.Belt 136 carries the slide above bins 138-141 for sorting as desired.For example, bin 138 could receive slide rejects, bin 139 might receiverandomly selected slides for quality control testing, and bins 140 and141 would be filled with slides for commercial sale.

Advantage of the Full Cover Sheet With Bridge

The integral cover sheet and porous bridge in accordance with thepresent invention reduces the number of slide components and offers amajor slide assembly advantage by eliminating the need for the slowerand waste prone process of placing discrete bridge units onto thepartially assembled slide. Further, the integral cover sheet minimizesperformance problems such as fluid leakage onto the ion-selectiveelectrodes and increased drop placement latitude.

Fluid leakage from the edge of the porous bridge of the integral coversheet will not increase the area of wetted electrode surface because theedge of the bridge is isolated from the ion-selective electrodes.Accordingly, test results will not be affected by such leakage.

Further, an integral cover sheet permits more accurate fluid access holeplacement than in the case where an ionic bridge must be placed on theslide as a discrete part. Accurate fluid access hole placement increasesdrop placement latitude.

Another advantage of the present invention is derived from the fact thatthe cover sheet is mechanically held to the slide by an ultrasonic sealaround its entire perimeter. Spacer web 36 is slightly thinner thanelectrodes 38 and 40 so that the cover sheet and electrodes are pressedtogether. Thus, the adhesive coating on the cover sheet serves primarilyas a fluid seal and does not have to be strong enough to hold the bridgeand electrodes together, thereby decreasing the risk of delamination ofthe bridge and fluid leakage thereunder.

The invention has been described in detail with particular reference topreferred embodiments thereof, but it will be understood that variationsand modifications can be effected within the spirit and scope of theinvention.

What is claimed is:
 1. In a device having an electrically insulativeframe and a pair of solid electrodes mounted on a surface of the framein a spaced-apart relationship for generating therein an electricalpotential having a predetermined relationship to the amount of ionicanalyte activity present in a contacting sample of an aqueous solution;the improvement comprising:an integral cover sheet extending over bothelectrodes and substantially the full surface of the frame upon whichthe electrodes are mounted, said cover sheet being formed of a nonporousmaterial and being bonded to the frame to secure the electrodestherebetween; a fluid access hole aligned with each electrode, extendingthrough said cover sheet for receiving a sample of the solution incontact with the electrodes; and an elongated ribbon of porous materialencapsulated in said cover sheet and extending at least between saidfluid access holes for providing ionic flow between solution samples ineach fluid access hole.
 2. The improvement as defined in claim 1 whereinsaid cover sheet nonporous material is a homogeneous plastic whichsubstantially surrounds said encapsulated porous material.
 3. Theimprovement as defined in claim 1 wherein said cover sheet nonporousmaterial comprises:a base of polystyrene, said elongated ribbon ofporous material being impressed into the surface of said base to leavean exposed ribbon surface; and a layer of polyethylene covering saidexposed ribbon surface.
 4. The improvement as defined by claim 1 furthercomprising a layer of adhesive material between said cover sheet andsaid electrodes for creating a seal around said fluid access holes toprevent solution sample from spreading between said cover sheet and saidelectrodes.
 5. In a device having an electrically insulative base and apair of solid electrodes mounted on the surface of the base in aspaced-apart relationship for generating therein an electrical potentialhaving a predetermined relationship to the amount of ionic analyteactivity present in a contacting sample of an aqueous solution; theimprovement comprising:a spacer web bonded to the base and having atleast one opening through which the electrodes extend, said spacer webbeing thinner than the electrodes so that the electrodes extend beyondthe surface of the spacer web; and an integral cover sheet extendingover both the two electrodes and substantially the full surface of saidspacer web, said cover sheet being formed of a nonporous material andbeing bonded to the spacer web to secure the electrodes between thecover sheet and the base under compressive force.
 6. The improvement asdefined in claim 6 further comprising:a fluid access hole aligned witheach electrode, extending through said cover sheet for receiving asample of the solution in contact with the electrodes; and a elongatedribbon of porous material encapsulated in said cover sheet and extendingat least between said fluid access holes for providing ionic flowbetween solution samples in each fluid access hole.
 7. The improvementas defined by claim 7 further comprising a layer of adhesive materialbetween said cover sheet and the electrodes for establishing a sealaround said fluid access holes to prevent solution sample from spreadingbetween said cover sheet and the electrodes.
 8. The improvement asdefined in claim 6 further comprising:a fluid access hole aligned witheach electrode, extending through said cover sheet for receiving asample of the solution in contact with the electrodes; and an elongatedribbon of porous material encapsulated in said cover sheet, extendingsubstantially the entire distance between opposed edges of said coversheet and aligned with said fluid access holes for providing ionic flowbetween solution samples in each fluid access hole.
 9. The improvementas defined in claim 1 further comprising at least one vent opening insaid cover sheet for permitting air trapped in said porous means betweensaid fluid access holes to escape as the solution in each fluid accesshole advances toward the solution in the other fluid access hole.
 10. Ina device having an electrically insulative frame and a pair of solidelectrodes mounted on a surface of the frame in a spaced-apartrelationship for generating therein an electrical potential having apredetermined relationship to the amount of ionic analyte activitypresent in a contacting sample of an aqueous solution; the improvementcomprising:an integral cover sheet extending over both electrodes andsubstantially the full surface of the frame upon which the electrodesare mounted, said cover sheet (1) being bonded to the frame to securethe electrodes therebetween and (2) being formed of a nonporous materialcomprising a base of polystyrene and a layer of polyethylene; a fluidaccess hole aligned with each electrode, extending through said coversheet for receiving a sample of the solution in contact with theelectrodes; and an elongated ribbon of porous material encapsulated insaid cover sheet, extending between said fluid access holes andsubstantially the entire distance between opposed edges of said coversheet for providing ionic flow between solution samples in each fluidaccess hole, said base impressed into the surface of, and covered bysaid layer of polyethylene.